Cell-line dependency in cerebral organoid induction: cautionary observations in Alzheimer’s disease patient-derived induced pluripotent stem cells

Ju Hyun Lee; Geon Yoo; Juhyun Choi; Si Hyung Park; Hyogeun Shin; Renuka Prasad; Yeunehee Lee; Mee Ryung Ahn; Il Joo Cho; Woong Sun

doi:10.1186/s13041-022-00928-5

Cell-line dependency in cerebral organoid induction: cautionary observations in Alzheimer’s disease patient-derived induced pluripotent stem cells

Ju Hyun Lee, Geon Yoo, Juhyun Choi, Si Hyung Park, Hyogeun Shin, Renuka Prasad, Yeunehee Lee, Mee Ryung Ahn, Il Joo Cho, Woong Sun

Department of Biomedical Sciences

Research output: Contribution to journal › Article › peer-review

1 Citation (Scopus)

Abstract

The cerebral organoid (CO) model has been used in the study of various neurodegenerative diseases owing to its physiological implications. However, the CO model may only be representative of certain clinical findings in affected patients, while some features are not recapitulated. In this study, we found that neurons in the CO model from patients with Alzheimer’s disease were less responsive to depolarization, in contrast to previous reports. This difference may be partly attributed to the variations in brain spatial identity depending on the genetic background of the induced pluripotent stem cells. Our current observation raises concerns that the phenotypes observed in the CO model need to be carefully evaluated for their clinical implications.

Original language	English
Article number	46
Journal	Molecular brain
Volume	15
Issue number	1
DOIs	https://doi.org/10.1186/s13041-022-00928-5
Publication status	Published - 2022 Dec

Bibliographical note

Funding Information:
This research was supported by the Brain Research Program through the National Research Foundation (NRF), which is funded by the Korean Ministry of Science, ICT & Future Planning (NRF-2021M3E5D9021368). This research was also supported by grants (19181MFDS424, 21181MFDS294) from Ministry of Food and Drug Safety in 2020 and 2021.

Publisher Copyright:
© 2022, The Author(s).

Keywords

Alzheimer’s diseases
Cell-to-cell variation
Cerebral organoid
Disease modeling

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience

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10.1186/s13041-022-00928-5

Cite this

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title = "Cell-line dependency in cerebral organoid induction: cautionary observations in Alzheimer{\textquoteright}s disease patient-derived induced pluripotent stem cells",

abstract = "The cerebral organoid (CO) model has been used in the study of various neurodegenerative diseases owing to its physiological implications. However, the CO model may only be representative of certain clinical findings in affected patients, while some features are not recapitulated. In this study, we found that neurons in the CO model from patients with Alzheimer{\textquoteright}s disease were less responsive to depolarization, in contrast to previous reports. This difference may be partly attributed to the variations in brain spatial identity depending on the genetic background of the induced pluripotent stem cells. Our current observation raises concerns that the phenotypes observed in the CO model need to be carefully evaluated for their clinical implications.",

keywords = "Alzheimer{\textquoteright}s diseases, Cell-to-cell variation, Cerebral organoid, Disease modeling",

author = "Lee, {Ju Hyun} and Geon Yoo and Juhyun Choi and Park, {Si Hyung} and Hyogeun Shin and Renuka Prasad and Yeunehee Lee and Ahn, {Mee Ryung} and Cho, {Il Joo} and Woong Sun",

note = "Funding Information: This research was supported by the Brain Research Program through the National Research Foundation (NRF), which is funded by the Korean Ministry of Science, ICT & Future Planning (NRF-2021M3E5D9021368). This research was also supported by grants (19181MFDS424, 21181MFDS294) from Ministry of Food and Drug Safety in 2020 and 2021. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1186/s13041-022-00928-5",

language = "English",

volume = "15",

journal = "Molecular brain",

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T2 - cautionary observations in Alzheimer’s disease patient-derived induced pluripotent stem cells

AU - Lee, Ju Hyun

AU - Yoo, Geon

AU - Choi, Juhyun

AU - Park, Si Hyung

AU - Shin, Hyogeun

AU - Prasad, Renuka

AU - Lee, Yeunehee

AU - Ahn, Mee Ryung

AU - Cho, Il Joo

AU - Sun, Woong

N1 - Funding Information: This research was supported by the Brain Research Program through the National Research Foundation (NRF), which is funded by the Korean Ministry of Science, ICT & Future Planning (NRF-2021M3E5D9021368). This research was also supported by grants (19181MFDS424, 21181MFDS294) from Ministry of Food and Drug Safety in 2020 and 2021. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12

Y1 - 2022/12

N2 - The cerebral organoid (CO) model has been used in the study of various neurodegenerative diseases owing to its physiological implications. However, the CO model may only be representative of certain clinical findings in affected patients, while some features are not recapitulated. In this study, we found that neurons in the CO model from patients with Alzheimer’s disease were less responsive to depolarization, in contrast to previous reports. This difference may be partly attributed to the variations in brain spatial identity depending on the genetic background of the induced pluripotent stem cells. Our current observation raises concerns that the phenotypes observed in the CO model need to be carefully evaluated for their clinical implications.

AB - The cerebral organoid (CO) model has been used in the study of various neurodegenerative diseases owing to its physiological implications. However, the CO model may only be representative of certain clinical findings in affected patients, while some features are not recapitulated. In this study, we found that neurons in the CO model from patients with Alzheimer’s disease were less responsive to depolarization, in contrast to previous reports. This difference may be partly attributed to the variations in brain spatial identity depending on the genetic background of the induced pluripotent stem cells. Our current observation raises concerns that the phenotypes observed in the CO model need to be carefully evaluated for their clinical implications.

KW - Alzheimer’s diseases

KW - Cell-to-cell variation

KW - Cerebral organoid

KW - Disease modeling

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Cell-line dependency in cerebral organoid induction: cautionary observations in Alzheimer’s disease patient-derived induced pluripotent stem cells

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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